Fully automated diagnostic analyzers are commercially available to perform chemical, and immunoassaying of biological fluids such as urine, blood serum, plasma, cerebrospinal fluid and the like. Generally, reactions between an analyte to be measured in the sample and reagents used during the assay result in generating some sort of signal that can be measured by the instrument, and from this signal the concentration of analyte in the patient sample may be calculated. Diagnostic analyzers generally employ a large number of various processing stations, where operations such as sample and reagent addition, mix, wash and separate, are performed. Within such analyzers, significant efforts are undertaken to insure that the accuracy of results obtained using automated clinical analyzers is not adversely affected by the various reagents and sample analysis procedures employed in performing different assay process steps, measuring techniques in particular. It is known that much effort has been given to the automated processing of complex immunoassays, including the challenges of maintaining high throughput and analytical accuracy. However, what has been overlooked in the prior art is that regardless of the emphasis placed on the accuracy, precision and throughput of immunoassays, some of the largest potential sources of error concern sample collection, handling methods and even the way the patient is handled before the sample is taken.
For example, if a patient's transferrin level is measured before surgery and after surgery, changes in levels can occur simply as a result of postsurgical stress and such changes might lead to erroneous conclusions that would not have been reached if an original sample had been available for retesting. In this instance, transferrin can fall after about 3 hours and ferritin starts to rise shortly afterwards. Thyroid hormone levels are also often repressed after surgery.
The dietary state of an individual may also lead to conclusions that would not have been reached if an original sample had been available for retesting. It is known that lipid levels change after a fatty meal; liver enzymes are affected by alcohol intake; the renin-aldosterone-angiotensin system is strongly affected by posture; and oral contraceptives have a pronounced effect on many binding proteins including those for thyroxine and cortisol.
Errors in interpretation of immunoassay results may also occur if a second patient sample is not collected correctly. A sample taken from the side on which a mastectomy has been recently done may not be as equally representative of a patient's health condition because of lymphostasis. In other instances, if a second patient sample is taken by needle and a primary sample tube used having a rubber stopper made of a plastic such as tris (2 butoxy-ethyl), the stopper itself may cause displacement of some drugs and other analytes from protein binding sites with consequent redistribution between erythrocytes and plasma. Furthermore, the vagaries involved in urine sample collection are well known.
In such instances, some of the largest potential sources of error concern specimen collection, handling methods and even the way the patient is handled before the specimen is taken. In addition, it may be desirable to repeat the same assay or to conduct other assays on a previously tested sample. For example, if the results of a previously performed assay fall materially outside the range of “expected” test results determined for a number of “normal” patient samples, it may be desirable to repeat the assay a second time for confirmation. For these reasons, original patient samples are often stored in a controlled environment for a period of time after an aliquot portion of the sample is analyzed.
In addition, assay results can serve as the basis for suggesting or requiring additional test assays on an aliquot of a previously tested sample, called reflex or spawned testing. Such reflex tests may be identified by algorithms which specify selection of subsequent assays based on results of previous assays, which concomitantly eliminates the need for human decision-making in selecting the tests, and minimizes the number of necessary tests that have to be run, thus leading to faster and more reliable diagnosis. Such features are tantamount to diagnostic efficiency and cost effectiveness and are popularly employed in clinical chemistry. It is therefore important that the very same patient sample be evaluated as opposed to an additional sample being re-taken for a patient, leading to another necessity to store an original patient sample.
Many commercially available systems for automated storage and retrieval of patient samples are based on Total Laboratory Automation (TLA). TLA systems typically utilize a conveyor system to transport the primary sample tube around the lab from instrument to instrument and then stores the tube in a huge refrigerator for future access. This concept is expensive, involves operator intervention and requires a significant amount of floor space to achieve.
A Storage Retrieval and Disposal System called SRS, produced by CRS Robotics Corporation, is a large stand-alone, automated system that archives primary sample tubes and retrieves them on request. An operator is required to take the sample to the analytical instrument and schedule the add-on tests. U.S. Pat. No. 6,068,437 is typical of such systems and discloses a storage area containing a plurality of racks for storing sample containers, the racks movable throughout the storage area to permit access to all of the racks from an opening in the upper end of the storage area. A robotic transfer apparatus is operable to insert and retrieve sample containers from selected racks in the storage area and move them between the storage area and a buffer area on the housing, as well as between the buffer area and a conveyor located adjacent the housing. The conveyor is of a type which transports sample carriers having a sample container therein, and the buffer area includes a rack for intermediate storage of sample containers.
Alternately, the patient sample may be stored on the analyzer itself in order to avoid the expense of such storage systems as well as to expedite the availability of a sample. The extensive efforts made to achieve these objectives are made clear by an examination of various aspects of modern analyzers.
U.S. Pat. No. 6,793,888 discloses a sample aliquot storage wheel with a pick-and-place mechanism for providing empty vessels and a sample pipettor for aspirating samples from sample tubes and aliquoting samples to empty vessels on the storage wheel. The sample aliquot storage unit has a chiller for controlling the storage environment on said sample storage wheel and means for driving the wheel to position sample vessels for access by the aliquoting station and transporting sample vessels containing sample aliquots back to the storage wheel.
U.S. Pat. No. 5,964,095 discloses a storage container holding an annular rack sealed by an enclosure. The enclosure includes an outer stationary toroid and a rotatable core. A robotic arm is adapted to move and is supported by the core. The robotic arm accesses an interior of the enclosure. An access portal allows removal and placement of thermolabile products constrained by a holder. The robotic arm accesses product and holder and embarks upon controlled freezing of the product and its location in the rack until subsequent retrieval. A computer stores in memory the location of all of the stored products. The robotic arm reads the product in storage to assure the correct product is being accessed.
U.S. Pat. No. 5,921,102 discloses a storage chamber with a carrier disposed inside the chamber for supporting a plurality of samples in a predetermined array, and an access port on the housing for enabling access to the chamber for insertion and retrieval of samples from the carrier. The access port includes an opening in the housing and a drive moves the carrier to juxtapose different samples to the access port. An insertion and removal mechanism alternately inserts and removes samples from the chamber via the access port during operation.
U.S. Pat. No. 5,233,844 discloses a storage chamber and a plurality of sample carriers in the form of annular shelves with pie-slice-shaped openings and disposed one below the other inside the chamber. A rotary drive is operatively connected to the carriers for rotating the carriers independently about a vertical axis. During operation, all openings of all the shelves (except a target shelf) are aligned vertically with an access opening and an insertion and removal mechanism serves to alternately insert and remove samples from the chamber via the opening. Such a system suffers from the disadvantage that all shelves must be rotated into alignment each time a different sample is desired to be extracted.
While these prior art sample storage and retrieval systems have a common objective, none provide the desirable advantage of enabling efficient, random-access to stored samples in combination with directly supplying of stored samples to an analyzer for re-testing.